Preferred Glucagon-like Peptide-1 Receptor Agonists in Adults With Type 2 Diabetes and Established Cardiovascular Disease or High Cardiovascular Risk: A Network Meta-analysis of Randomized Trials

IF 2.7 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Canadian Journal of Diabetes Pub Date : 2026-08-01 Epub Date: 2026-04-10 DOI:10.1016/j.jcjd.2026.04.001

Mustafa Abomohsen MD, Mohamed Rifai MD, Ahmed Farid Gadelmawla MD, Hamzah M. Alghzawi MD, Mohamed S. Elgendy MBBCh, Hager Mohamed Bakr MBBCh, Adam Friedman MD, Iyad Y. Idries MD

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引用次数: 0

Abstract

The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain. PubMed, Embase, Web of Science, Scopus, and CENTRAL were searched from inception to December 20, 2025, for randomized controlled trials. We conducted a frequentist random-effects network meta-analysis and reported risk ratios (RRs) with 95% confidence intervals (CIs). Treatments were ranked using P-scores. Regimens were analyzed as individual agents, including albiglutide, dulaglutide, efpeglenatide, exenatide extended release, ITCA 650, liraglutide, lixisenatide, subcutaneous semaglutide, oral semaglutide, tirzepatide, and placebo. Eleven trials (n=83,215) were included. In the 3-point major adverse CV events (MACE) network (11 trials, 11 regimens), heterogeneity and inconsistency were absent (I²=0%, τ²=0). MACE rate was reduced with subcutaneous semaglutide (RR 0.74, 95% CI 0.58 to 0.94), efpeglenatide (RR 0.76, 95% CI 0.61 to 0.94), and albiglutide (RR 0.79, 95% CI 0.69 to 0.91); tirzepatide, oral semaglutide, liraglutide, and dulaglutide were also significantly reduced compared with placebo. Top ranked were subcutaneous semaglutide (P-score 0.87), efpeglenatide (0.84), and albiglutide (0.80). No regimen significantly reduced all-cause or CV death compared with placebo. Stroke was reduced with tirzepatide (RR 0.71, 95% CI 0.54 to 0.93) and dulaglutide (RR 0.77, 95% CI 0.63 to 0.95) vs placebo. Discontinuation and gastrointestinal discontinuation were higher with subcutaneous semaglutide, oral semaglutide, lixisenatide, and ITCA 650. Several GLP-1–based therapies reduced MACE vs placebo, with 3-point MACE emerging as the most consistent efficacy signal. Overall, these findings support guideline-based use of GLP-1 RAs in high-risk T2D while highlighting the need for individualized treatment selection.

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首选GLP-1受体激动剂治疗伴有心血管疾病或高危心血管疾病的2型糖尿病：随机试验的网络荟萃分析

背景：GLP-1受体激动剂（GLP-1RAs）在2型糖尿病（T2D）和已确诊心血管疾病（CVD）或高危心血管疾病患者的心血管（CV）疗效和安全性的比较仍不确定。方法：检索PubMed、Embase、Web of Science、Scopus和CENTRAL，检索从成立到2025年12月20日的随机对照试验。我们进行了频率随机效应网络荟萃分析，并报告了95%置信区间（ci）的风险比（rr）。使用p分数对治疗进行排名。将方案作为单个药物进行分析，包括阿比鲁肽、杜拉鲁肽、依佩格内酯、艾塞那肽ER、ITCA 650、利拉鲁肽、利昔塞那肽、皮下塞马鲁肽、口服塞马鲁肽、替西帕肽和安慰剂。结果：纳入11项试验（n= 83215）。在三点主要不良CV事件（MACE）网络（11项试验；11个方案）中，不存在异质性和不一致性（I2=0%; τ2=0）。皮下注射semaglutide （RR 0.74, 95% CI 0.58-0.94）、efpeglenide（0.76, 0.61-0.94）和albiglutide（0.79, 0.69-0.91）可降低MACE；与安慰剂相比，替西帕肽、口服西马鲁肽、利拉鲁肽和杜拉鲁肽的疗效也显著。排名靠前的是semaglutide SC （p值0.87）、efpeglenatide （p值0.84）和albiglutide （p值0.80）。与安慰剂相比，没有方案显著降低全因或CV死亡。与安慰剂相比，替西帕肽（RR = 0.71, 0.54-0.93）和杜拉鲁肽（RR = 0.77, 0.63-0.95）可减少卒中。皮下塞马鲁肽、口服塞马鲁肽、利昔那肽和ITCA 650的停药率和胃肠道停药率较高。结论：几种基于glp -1的治疗方法与安慰剂相比降低了MACE，其中3点MACE是最一致的疗效信号。总的来说，这些发现支持GLP-1 RAs在高危T2DM中基于指南的使用，同时强调了个性化治疗选择的必要性。

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来源期刊

Canadian Journal of Diabetes ENDOCRINOLOGY & METABOLISM-

CiteScore

4.80

自引率

4.00%

发文量

130

审稿时长

54 days

期刊介绍： The Canadian Journal of Diabetes is Canada''s only diabetes-oriented, peer-reviewed, interdisciplinary journal for diabetes health-care professionals. Published bimonthly, the Canadian Journal of Diabetes contains original articles; reviews; case reports; shorter articles such as Perspectives in Practice, Practical Diabetes and Innovations in Diabetes Care; Diabetes Dilemmas and Letters to the Editor.